YOU, 2019. Meta-Analysis On The Efficacy and Safety of Traditional Chinese Medicine As Adjuvant Therapy For Refractory Androgenetic Alopecia

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Review Article

Meta-Analysis on the Efficacy and Safety of Traditional


Chinese Medicine as Adjuvant Therapy for Refractory
Androgenetic Alopecia

Qiang You ,1,2 Lan Li ,3 Xiao Ma ,1 Tian Gao ,4 Suqin Xiong ,1 Yufen Yan ,1
Hao Fang ,1 Fengqing Li,1 Hongping Chen ,1 and Youping Liu 1
1
Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
2
The Affiliated Hospital, Southwest Medical University, Luzhou, China
3
Department of Nursing, Southwest Medical University, Luzhou, China
4
The Affiliated Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, China

Correspondence should be addressed to Hongping Chen; chen_hongping@126.com and Youping Liu; youpingliu@cdutcm.edu.cn

Qiang You and Lan Li contributed equally to this work.

Received 12 April 2019; Revised 5 July 2019; Accepted 7 July 2019; Published 31 October 2019

Academic Editor: Jenny M. Wilkinson

Copyright © 2019 Qiang You et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.

Objective. Traditional Chinese medicine (TCM) therapies have been widely used for the treatment of androgenetic alopecia (AGA)
for thousands of years. We conducted a meta-analysis to evaluate the curative efficacy and safety of TCM for treating AGA.
Methods. Randomized controlled trials (RCTs) of TCM for the treatment of AGA through March 2019 were systematically
identified in 4 English databases, namely, PubMed, Cochrane Library, EMBASE, and Web of Science, and 4 Chinese databases,
namely, Sino-Med, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP),
and WanFang. Quality assessment and data analysis were performed by Review Manager 5.3.5, and Stata 15.1 was used to cope
with publication bias. Results. 30 RCTs involving 2615 patients were randomly divided into a TCM group and a conventional
medicine (CM) group. The results showed that the total efficacy rate (TER) of the TCM group was significantly higher than that of
the control group (OR � 3.34, 95% CI � 2.75–4.05, P < 0.00001). The total symptom score (TSS) of the TCM group was markedly
reduced when compared with the CM group (SMD � − 0.86; 95% CI � − 1.19, − 0.53; P < 0.00001). The microelement levels (Fe2+,
Zn2+, and Cu2+) in hair were significantly improved when complemented with TCM therapy. In addition, no significant dif-
ferences were observed between the two groups in terms of adverse events (OR � 0.55, 95% CI � 0.29–1.05, P � 0.07). Conclusions.
In view of the effectiveness and safety of TCM, the present meta-analysis suggests that TCM could be recommended as an effective
and safe adjuvant therapy for the treatment of AGA by improving the TER, symptoms, serum testosterone levels, and mi-
croelement levels. However, long-term and higher-quality RCTs are needed to overcome the limitations of the selected studies and
more precisely interrogate the efficacy and safety of TCM.

1. Introduction psyche [2]. It was reported that at the age of fifty, the
prevalence of male AGA was approximately 50% [3] and
Androgenetic alopecia, or male-pattern baldness, is one of increased with age [4]. In China alone, hair loss affects more
the most common types of hair loss in both men and women, than 100 million men, and the aging of the rapidly growing
affecting approximately 0.2–2% of the world’s population global population is likely to aggravate this situation [5].
[1, 2]. Even if medically regarded as a relatively mild skin Modern medical research suggests that AGA is char-
disease, alopecia leads to significant negative effects on the acterized by an autosomal dominant polygenic inheritance
quality of life because of the importance of hair in people’s of alopecia and is highly associated with androgen-
2 Evidence-Based Complementary and Alternative Medicine

dependent miniaturization of scalp hair follicles and that and Technology Periodical Database (VIP), and Chinese
dihydrotestosterone disorder is an important pathogenic Biomedical (Sino-Med) through March 2019. Because TCM
factor [6]. Although much research has been devoted to is mainly used in China, we searched these aforementioned
antialopecia drugs, only two drugs, finasteride and mi- Chinese electronic databases to obtain as many clinical trials
noxidil, have been approved by the FDA. Finasteride, a as possible. The search languages were restricted to Chinese
specific inhibitor of 5α-reductase, shows high irreversible and English. For the English databases, we used the fol-
binding affinity to the enzyme and inhibits the conversion of lowing search strategies: subject terms plus its entry terms.
testosterone into highly active dihydrotestosterone, which For the Chinese databases, we used subject terms � (“Zhong
provides an effective target for AGA treatment. However, Yao”) and title � (“Tuo Fa” or “Ban Tu” or “Diao Fa”).
three percent of patients experience sexual dysfunction [7]. Moreover, we manually searched articles meeting our in-
These symptoms include decreased libido, diminished sexual clusion criteria from other sources, but not obtained from
function (impotence), decreased ejaculation volume, and the above 8 databases. Eligible studies were independently
ejaculation disorder [8]. Generally, minoxidil is an estab- screened out by two reviewers. When a discrepancy occurred
lished therapy for AGA in both men [9, 10] and women [11]. between the two investigators, it was resolved by discussion.
Although the exact mechanism is unclear, contact dermatitis The detailed search strategy for the aforementioned English
[12], skin irritation [13], dizziness, and tachycardia [14] have databases is shown in Table 1.
been reported. In addition, once the medication is dis-
continued, hair loss persists. Specifically, the efficacy and
safety of the two drugs are unsatisfactory. Thus, research into 2.2. Article Inclusion and Data Extraction. The systematic
effective treatments that can enhance the efficacy of finas- review was conducted on the basis of the Preferred
teride and minoxidil is of great social and clinical Reporting Items for Systematic Review and Meta-Analyses
significance. (PRISMA) Statement. We selected eligible studies based on
Currently, an increasing number of AGA patients in East the following inclusion criteria: (1) the TCM groups were
Asia have resorted to seeking effective and safe comple- treated with TCM regardless of formulation (lotion, pill,
mentary therapies for AGA from traditional Chinese decoction, or capsule); (2) the control groups were treated
medicine (TCM). Traditional Chinese herbal formulas with placebo or conventional therapy; and (3) the TER and
(CHFs) with fixed ingredients, recorded in the ancient total symptom score (TSS) were used as the primary out-
Chinese classic medical books, have shown striking effects in come by referring to guidelines, consensus views, or the
the treatment of some chronic diseases such as AGA, evaluation criteria. The exclusion criteria were as follows: (1)
chronic hepatitis, chronic gastritis, cerebrovascular diseases, non-RCTs; (2) the TCM groups received the combination
and diabetes [15, 16]. TCM used for hair loss dates back to treatment of TCM and acupuncture therapy, or the TCM
the Qin Dynasty two thousand years ago. After thousands of groups were treated with simple plant extracts; (3) studies
years of development, ancient Chinese medicine has accu- did not have control groups or control subjects who received
mulated a large number of effective CHFs and rich expe- TCM treatment including herbal medicine, acupuncture, or
rience in treating AGA. In recent years, an increasing acupoint injection therapy; (4) hair loss induced by che-
number of clinical studies have indicated that the conven- motherapy or non-AGA; and (5) systematic review, im-
tional medicines (CM) have been significantly improved portant data reports, and case reports. Two reviewers (Yufen
when complemented with TCM, and abundant evidence has Yan and Suqin Xiong) independently extracted the data,
demonstrated that CHFs with various types of medicinal including the following contents: first author’s last name,
ingredients can substantially promote the recovery from year of publication, sample size, age, TCM name, CM name,
AGA and significantly lower adverse event rates and re- duration of treatment, dose, main outcomes, and adverse
currence rates. However, the popularizing rate of TCM events.
therapies beyond China is limited, and there is still a lack of
reliable evidence that systematically reviews the clinical 2.3. Quality Assessment. Two reviewers (Fengqing Li and
efficacy and safety of TCM. Therefore, it is necessary to Hao Fang) independently evaluated the methodological
rigorously conduct a systematic review and meta-analysis to qualities of the trials according to the Cochrane Manual [17].
assess the efficacy and safety of TCM for AGA to provide a The risk of bias consisted of seven items: selection bias,
reference for the clinical and rational usage of drugs and performance bias, detection bias, attrition bias, reporting
individual treatment in an objective manner. bias, and other bias. Each item was classified into low bias
risk, high bias risk, and unclear bias risk. Disagreements
2. Methods between the reviewers were settled through discussion.
2.1. Search Strategy. The protocol has been registered in
PROSPERO (ID: CRD42019117139). Available online at 2.4. Data Analysis. In this review, the statistical analysis was
http://www.crd.york.ac.uk/PROSPERO/display_record.asp? conducted by Reviewer Manager (version 5.3.5), and we
ID�CRD42019117139. The databases from which we re- used OR with 95% CI to analyze dichotomous data, whereas
trieved studies in this review included PubMed, WanFang, the continuous data were presented as MD or SMD with 95%
EMBASE, Web of Science, Cochrane Library, China Na- CI. The data were merged according to the Mantel–Haenszel
tional Knowledge Infrastructure (CNKI), Chinese Science (fixed-effects) model and the DerSimonian and Laird
Evidence-Based Complementary and Alternative Medicine 3

Table 1: Search strategy of the English databases.


Database Search term A Search term B Strategy
[Title/abstract] � (traditional Chinese medicine
OR Zhong Yi Xue OR Zhong yao OR herbal
medicine OR phytotherapy OR Chinese [Title/abstract] � (alopecia OR Baldness∗ OR Term A and Term
PubMed
medicine OR phytotherapies OR Chinese herbal hair Loss∗ OR calvities OR balding OR AGA) B
compound OR Chinese herbal formula∗ OR
Chinese compound formula∗ OR TCM)
[Title/abstract] � (traditional Chinese medicine
OR Zhong Yi Xue OR Zhong yao OR herbal
medicine OR phytotherapy OR Chinese [Title/abstract] � (alopecia OR Baldness∗ OR Term A and Term
EMBASE
medicine OR phytotherapies OR Chinese herbal hair Loss∗ OR calvities OR balding OR AGA) B
compound OR Chinese herbal formula∗ OR
Chinese compound formula∗ OR TCM)
TS � (“traditional Chinese medicine” or “herbal
medicine” or “Zhong Yi Xue” or “Zhong Yao” or
“phytotherapy” or “Chinese medicine” or TS � (“alopecia∗ ” or “baldness∗ ” or “calvities” or Term A and Term
Web of Science
“phytotherapies” or “Chinese herbal “Hair Loss∗ ” or “balding∗ ” or “AGA”) B
compound∗ ” or “Chinese herbal formula∗ ” or
“Chinese compound formula∗ ” or “TCM”)
[Title/abstract] � (traditional Chinese medicine
OR Zhong Yi Xue OR Zhong yao OR herbal
Cochrane medicine OR phytotherapy OR Chinese [Title] � (alopecia OR baldness∗ OR hair Loss∗ Term A and Term
library medicine OR phytotherapies OR Chinese herbal OR calvities OR balding OR AGA) B
compound OR Chinese herbal formula∗ OR
Chinese compound formula∗ OR TCM)

(random-effects) model [18]. Heterogeneity between the group comprised lotion (n � 3), decoction (n � 25), capsule
studies was determined by the chi-square test. With the I2 (n � 1), and pill (n � 1), and the interventions of the control
statistic, an I2 < 25% indicated that heterogeneity may not be groups included finasteride, minoxidil, ketoconazole,
important, values between 25% and 50% represented a cystine, vitamins, and selenium disulfide. Eighteen trials
moderate inconsistency, and I2 > 50% suggested severe het- reported the specific number of adverse events. Generally,
erogeneity. We defined P ≥ 0.1 and I2 < 50 as indication that the basic characteristics of the 2615 patients were consis-
the results have good agreement, and the fixed-effects model tent, and no significant differences were found before the
would be used, while I2 > 50% was an indicator of significant intervention. The literature search process is shown in
heterogeneity among trials. Then, we used a random-effects Figure 1, and the general characteristics of the selected
model to estimate the pooled results to minimize the influence studies are listed in Table 2.
of potential clinical heterogeneity. All the statistical tests were
two-tailed, and the differences were statistically significant at
3.2. Methodological Quality Assessment. The specific ran-
P < 0.05. Sensitivity analyses were performed to evaluate the
domized methods were detailed in 9 studies [25, 27, 36–38,
robustness of the merged results by removing individual
43, 49, 50, 53] which used random number tables or
studies. Egger’s test was used to evaluate publication bias.
computer or sealed envelopes in the assessment of selection
bias. Therefore, we considered them to be low risk. The
3. Results remaining 21 studies did not offer any detailed information
3.1. Search Results and Study Characteristics. In total, 1048 regarding the generation of random sequences. Almost all
papers were obtained from a database search (Web of Science the studies failed to give the specific allocation conceal-
(n � 48), Cochrane Library (n � 10), EMBASE (n � 61), ment, performance bias, or detection bias. Attrition bias
PubMed (n � 50), CNKI (n � 259), Sino-Med (n � 331), VIP was at high risk in four documents [25, 39, 41, 50] due to
(n � 221), and WanFang (n � 68)), of which 520 duplicated the number of dropouts and failure to follow up the process
publications were removed. A total 397 citations of irrelevant of treatment. In general, the quality of the 30 studies was
topics were excluded after reading the titles and abstracts low or remained indistinct because of the high ratio of the
(irrelevant studies (n � 280), review studies (n � 85), animal unclear risk of biases in most of the studies. The particular
test studies (n � 32)), and 101 other studies were ruled out results of bias assessment are summarized in Figure 2.
following a screening of the full text (irrelevant interventions
(n � 66), non-RCT studies (n � 15), and conference papers 3.3. Primary Outcome
(n � 20)). Finally, according to the inclusion criteria, 30 RCTs
published between 2008 and 2018 involving 2615 AGA 3.3.1. Total Efficacy Rate (TER). All the studies reported the
patients were eligible. The sample size was 40 to 185, with a TER involving 1396 patients in the TCM group and 1219
significant age difference. The dosage forms of the TCM patients in the CM group. The heterogeneity test (P � 0.85,
4 Evidence-Based Complementary and Alternative Medicine

Identification
Records identified through database searching (n = 1048)
Additional records
Web of science (n = 48), Cochrane Library (n = 10),
identified through other
Embase (n = 61), PubMed (n = 50), CNKI (n = 259),
sources (n = 0)
Sino-Med (n = 331), VIP (n = 221), and WanFang (n = 68)
Screening

Records after duplicates Reading titles and abstracts


removed (n = 528) Irrelevant studies (n = 280)
Review studies (n = 85)
Animal test studies (n = 32)

Records screened (n = 131)


Eligibility

Reading the full text


Irrelevant interventions (n = 66)
Articles remaining after Not RCT studies (n = 15)
reading the full text (n = 30) Conference papers (n = 20)
Included

Studies included in
quantitative synthesis
(meta-analysis) (n = 30)

Figure 1: Flowchart of study selection.

I2 � 0%) suggested that a fixed-effects model was more indicated that in comparison with the CM, the addition of
suitable. The results showed a significant difference between TCM therapy strikingly improved the Fe2+ (MD � 2.65, 95%
the TCM and CM groups, which indicated that patients in CI � 2.63, 2.98, P < 0.00001), Zn2+ (MD � 18.89, 95%
the TCM group benefitted more than those in the CM group CI � 10.68, 27.10, P < 0.00001), and Cu2+ levels (MD � 0.76,
(OR � 3.34, 95% CI � 2.75–4.05, P < 0.00001), and no dif- 95% CI � 0.51, 1.01, P < 0.00001). However, no statistic
ference was found between the subgroups (P � 0.52, difference was observed between the TCM and CM groups
I2 � 0%), as shown in Figure 3. in terms of the Ca2+ level (MD � 17.98, 95% CI � − 2.17,
38.14, P � 0.008), as shown in Figure 6.
3.3.2. TSS. Seven studies [29, 30, 36, 38, 41, 42, 50] reported
the TSS. Because of significant heterogeneity, a standardized
mean difference (SMD) with a random-effects model was 3.5. Adverse Events. Eighteen RCTs reported the specific
employed to synthesize the data (P � 0.002, I2 � 71%). The number of adverse events involving 39 patients in the two
results suggested that the TSS of the TCM group was re- groups (15 cases for the TCM groups and 24 cases for the
duced more effectively than that of the CM group control groups). Nine of the 18 studies reported adverse
(SMD � − 0.86; 95% CI � − 1.19, − 0.53; P < 0.00001), as events in their trial [24, 27, 33, 35, 38, 41, 49–51]. The main
shown in Figure 4. adverse reactions were dermatitis (pruritus and epi-
folliculitis) and slight gastrointestinal upset including
3.4. Secondary Outcome nausea, vomiting, inappetence, and diarrhea. No serious
adverse events (such as liver injury and kidney damage)
3.4.1. Common Symptoms. Several studies reported the were mentioned in any of the studies. One study [27]
common symptoms comprising itchy scalp (n � 6), greasy reported that four patients in the control group experi-
scalp (n � 5), and dandruff (n � 6). The results suggested that enced hypaphrodisia after taking finasteride (4/59, 10%)
the addition of TCM significantly improved the itchy scalp and were relieved after drug withdrawal. No adverse re-
level (SMD � − 2.60, 95% CI � − 3.38, − 1.33, P < 0.0001), actions occurred in another nine trials during the course of
greasy scalp level (SMD � − 3.86, 95% CI � − 5.77, − 1.95, treatment [8, 25, 26, 29, 30, 36, 40, 42, 45]. However, we
P < 0.0001), and dandruff level (SMD � − 2.63, 95% failed to report the adverse events in the remaining 12
CI � − 3.83, − 1.43, P < 0.0001) when compared with the studies due to the absence of complete data. This meta-
control groups, as shown in Figure 5. analysis indicated that no heterogeneity was found
(P � 0.63, I2 � 0%), and there was no significant difference
3.4.2. Microelement Levels (Ca2+, Fe2+, Zn2+, and Cu2+). between the TCM and the CM groups in terms of the
The microelement levels of hair including Ca2+, Fe2+, Zn2+, adverse events (OR � 0.55, 95% CI � 0.29–1.05, P � 0.07).
and Cu2+ were determined in two trials [34, 37]. The results Although no statistical significance was observed, there was
Table 2: The general characteristics of the 30 trials.
Age Adverse
Sample Intervention
(mean or Diagnostic criteria/ Duration of use reactions
Study size Main outcome
range) classification [19–23] (months)
(T/C) T C T C
T/C
Guiding principles for clinical research of ShengFa
Yang et al. [24] 32/30 20–40 Placebo (5 ml, qod local) 12 3 3 ①
new Chinese medicine Lotion (5 ml, qod, local)
Chien et al. [25] 20/20 39.85 ± 8.77/35.30 ± 7.19 Hamilton–Norwood BeauTop (2.4 g, bid, po) Placebo (2.4 g, bid, po) 6 0 0 ①
YuFaYe
Liang et al. [26] 45/48 21.3 ± 1.58/21.1 ± 1.04 Clinical dermatology Placebo (4 ml, bid, local) 4 0 0 ①
Lotion (4 ml, bid, local)
YiRen QuShi
Yang [27] 40/40 28.4 ± 6.2/28.7 ± 6.0 Hamilton–Norwood (II-VI) Finasteride (1 mg, qd, po) 3 0 4 ①②③④
Decoction (1 dose, qd, po)
TuoFaFang
Wu et al. [28] 84/74 29.34 ± 7.13/28.41 ± 6.64 Clinical dermatology Finasteride (1 mg, qd, po) 3 NR NR ①
Decoction (150 ml, bid, po)
Clinical dermatology QuShi ShengFaFang
Dai [29] 67/44 20–45 Finasteride (1 mg, qd, po) 3 0 0 ①②③④
Hamilton–Norwood (II-VI) Decoction (1 dose, qd, po)
Clinical dermatology QuShi ShengFa
Wu et al. [30] 58/36 27.8 ± 5.9/28.47 ± 5.13 Finasteride (1 mg, qd, po) 6 0 0 ①⑤
Hamilton–Norwood (II-VI) Decoction (1 dose, qd, po)
QuZhi GuTuoYin
Sui [31] 46/46 26.43 ± 7.01/26.54 ± 6.62 Clinical dermatology Finasteride (1 mg, qd, po) 3 NR NR ①
Decoction (200 ml, bid, po)
Clinical diagnosis and treatment of TCM QuShi JianFaYin
Wang et al. [32] 40/40 27.32 ± 6.06/27.14 ± 5.58 Finasteride (1 mg, qd, po) 6 NR NR ①
dermatology Decoction (200 ml, bid, po)
Chinese guidelines for the diagnosis and ShengFa Pill
Li et al. [33] 112/73 26.42 ± 5.63/25.87 ± 6.12 Finasteride (1 mg, qd, po) 6 3 0 ①
treatment of androgenetic alopecia Decoction (1 dose, qd, po)
QuZhi ShengFaYin Decoction
Etiology, diagnosis, and treatment of
Wang and Zhang [34] 43/43 29.7 ± 8.5/28.6 ± 8.3 (150 ml, bid, po) Finasteride (1 mg, qd, po) 6 NR NR ①②③④⑥
androgenetic alopecia
Evidence-Based Complementary and Alternative Medicine

Finasteride (1 mg, qd, po)


DiHuang ShengFaLing Decoction
He and Liang [35] 51/49 29.54 ± 5.79/29.92 ± 6.43 Hamilton (II–V) 2%–5% minoxidil (1 ml, bid, local) 9 0 2 ①
(5 g, bid, po)
Mo [36] 35/33 18–50 Clinical dermatology QuZhi ShengFa Lotion (50 ml, qid, local) 5% minoxidil (1 ml, bid, local) 6 0 0 ①②③④
JiaWei ErZhiWan Decoction
Zhang [37] 42/42 20–32 Clinical dermatology (150 ml, bid, po) 5% minoxidil (1 ml, bid, local) 6 NR NR ①⑥
5% minoxidil (1 ml, bid, local)
YiShen ShengFaTang Decoction
Clinical dermatology
Liu and sun [38] 50/50 28.35 ± 4.52/28.23 ± 4.35 (150 ml, bid, po) 5% minoxidil (1 ml, bid, local) 3 1 1 ①
Hamilton (II–V)
5% minoxidil (1 ml, bid, local)
MAGA (I-III) Gao Fang Decoction (20 ml, bid, po)
Bao et al. [39] 29/28 27.96 ± 10.5/29.18 ± 9.787 5% minoxidil (1 ml, bid, local) 4 NR NR ①
Ludwig (I-III) 5% minoxidil (1 ml, bid, local)
BuShen ZiYing Fang Decoction
Clinical dermatology (1 dose, qd, po) Finasteride (1 mg, qd, po)
Wang [40] 30/28 35.27 ± 5.74/35.57 ± 5.98 6 0 0 ①②③④
Hamilton–Norwood (II-VI) Finasteride (1 mg, qd, po) 5% minoxidil (1 ml, bid, local)
5% minoxidil (1 ml, bid, local)
ZhaQu PinWeiSan He Er ZhiWan
Finasteride (1 mg, qd, po)
Xiang [41] 40/40 18–50 Hamilton–Norwood (II-VI) Decoction (150 ml, tid, po) 9 2 4 ①⑤
5% minoxidil (1 ml, bid, local)
5% minoxidil (1 ml, bid, local)
VitaminB2 (5 mg, tid, po)
Xiang [42] 35/28 28.3 ± 6.7/30.5 ± 5.3 Clinical dermatology, Norwood-Ludwig Tanshinone Capsule (2#, tid, po) 3 0 0 ①⑤
Vitamin B6 (10 mg, tid, po)
Qibao beards folk prescription VitaminB6 (10 mg, tid, po)
Lin [43] 43/43 59.44 ± 2.57/58.16 ± 2.98 Clinical dermatology 4 NR NR ①②③④
Decoction (200 ml, bid, po) Cystine (50 mg, tid, po)
Integrated Chinese and western JiaWei HuangLian EJiao Decoction VitaminB6 (10 mg, tid, po)
Gong [44] 46/46 20–48 3 NR NR ①
medicine dermatology (200 ml, bid, po) Cystine (50 mg, tid, po)
GuShen ShengFaTang Decoction VitaminB6 (10 mg, tid, po)
Xi et al. [45] 45/35 30.1 ± 12.8/29.7 ± 11.6 Clinical dermatology 3 0 0 ①
(150 ml, bid, po) Cystine (50 mg, tid, po)
ZiNi ZiShen YangXue ShengFaTang VitaminB6 (10 mg, tid, po)
Xia and Liu [46] 30/30 25–51 Clinical dermatology Decoction (300 ml, bid, po) Cystine (50 mg, tid, po) 6 NR NR ①
5% minoxidil (1 ml, bid, local) 5% minoxidil (1 ml, bid, local)
5
6

Table 2: Continued.
Age Adverse
Sample Intervention
(mean or Diagnostic criteria/ Duration of use reactions
Study size Main outcome
range) classification [19–23] (months)
(T/C) T C T C
T/C
Clinical diagnosis and treatment YangXue ShengFa HeJi VitaminB6 (10 mg, tid, po)
Ye and Qi [47] 25/25 17–50 3 NR NR ①
of TCM dermatology Decoction (30 ml, tid, po) Cystine (50 mg, tid, po)
QuZhi ShengFa VitaminB6 (10 mg, tid, po)
Xi et al. [48] 36/30 29.3 ± 4.7/29.6 ± 4.2 Hamilton (II-IV) 3 NR NR ①
Pill (9 g, tid, po) Cystine (50 mg, tid, po)
Clinical diagnosis and treatment Fukang mixture VitaminB6 (20 mg, tid, po)
Wang et al. [49] 83/45 26/29 4 2 0 ①
of TCM dermatology Decoction (20 ml, tid, po) Cystine (10 mg, tid, po)
VitaminB6 (10 mg, tid, po)
30.62 ± 10.04/ ShengFa Decoction (20 ml, tid, po)
Fang [50] 36/36 Clinical dermatology Cystine (50 mg, tid, po) 6 1 2 ①②④⑤
29.94 ± 9.46 5% minoxidil (1 ml, bid, local)
5% minoxidil (1 ml, bid, local)
21-Super-Vita (0.7 g, tid, po)
Guiding principles for clinical JianWei YiShen, QuShi ShengFa
Xie [51] 33/32 45.5 ± 1.2/45.6 ± 1.4 Cystine (100 mg, tid, po) 3 3 8 ①
research of new Chinese medicine Decoction (bid, po)
2%KCZ (biw)
21-Super-Vita (0.7 g, tid, po)
Integrated Chinese and western Quzhi Fangtuo shengfa ying
Liu [52] 60/60 42 ± 7.9/42 ± 7.8 Cystine (100 mg, tid, po) 3 NR NR ①
medicine dermatology Decoction (100 ml, biw, local)
2%KCZ (biw)
ShengFa Ting Decoction (biw, local)
Xu et al. [53] 47/48 32.15 ± 4.62/31.21 ± 4.16 Clinical dermatology Selenium sulfide (biw) 3 0 0 ①
Selenium sulfide (biw)
T: experimental group; C: control group; KCZ: ketoconazole; NR: no record; ①: total efficacy rate; ②: itchy scalp level; ③: greasy scalp level; ④: dandruff level; ⑤: total symptom score; and ⑥: microelement level.
Evidence-Based Complementary and Alternative Medicine
Evidence-Based Complementary and Alternative Medicine 7

an obvious trend of a decreased total adverse events rate in finasteride and minoxidil is a crucial issue for medical
the TCM group (15/845, 1.8%) when compared with the investigators worldwide.
CM group (24/652, 3.7%). Therefore, the addition of TCM, Chinese classic herbal formulas documented in the
to some extent, reduced the total adverse events rate, as ancient Chinese medical literature have been widely used
shown in Figure 7. for AGA for thousands of years. Examples include “Yellow
Emperor’s Inner Classic” during the Warring States Pe-
riod (457–221 BC) [59], “Treatise on Febrile Diseases”
3.6. Sensitivity Analysis. Stata 15.1 was applied to the sen- during the Three Kingdoms period (219 AD), and
sitivity analysis of the main outcomes comprising TER and “Compendium of Materia Medica” during the Ming
TSS. The results suggested that removing any one study of Dynasty (1552–1578 AD) [38]. With long-term clinical
each outcome had no significant effect on the overall results, experience, the ancient TCM physicians found that the
indicating that the results of this meta-analysis were reliable, aetiological agent of AGA were mainly resulted from
as shown in Figure 8. blood-heat with dry wind, spleen-stomach with damp-
ness-heat, and liver and kidney deficiency [38], and these
physicians obtained extensive effective CHFs for the
3.7. Publication Bias. Stata15.1 software was used to detect treatment of AGA. Compared with the single therapeutic
the possible publication bias of the primary outcome, and approach of CM, TCM lays more emphasis on the in-
the trim and filling method was conducted to cope with tegrality and multitarget effects of therapy. In recent years,
striking publication bias if the P < 0.05. The result of Egger’s TCM therapies have played a significant role in modern
test suggested that significant publication bias was observed comprehensive treatment. An increasing number of
in terms of TER (P > |t| � 0.013, 95% CI � 0.34 to 2.6). Then, studies have confirmed its unique effect and role in
trim and filling methods were employed to evaluate the compensating for the deficiencies of CM. Both the de-
reliability of the results affected by significant publication coction and lotion treatment of TCM have exhibited
bias [54]. After running the iteration, seven studies marked satisfactory effects in easing itchy scalp, greasy scalp,
with squares were filled into the funnel plot. However, the dandruff, and hair loss [27, 29, 34, 36, 43, 50] through the
OR and 95% CI after the trim and filling method promotion of blood circulation, removing blood stasis
(OR � 2.86; 95% CI � 2.37–3.44) were consistent with the [31, 39, 60], tonifying kidney and liver [33, 43], clearing
previous result (OR � 3.34, 95% CI � 2.75–4.05), indicating heat and removing toxicity [35], calming the heart and
that the result was stable without the flip, as shown in tranquilizing the mind [33], increasing the microelement
Figure 9. levels of the hair [34, 37], and downregulating the serum
testosterone level [25, 34, 42]. A 2014 meta-analysis [61]
4. Discussion was undertaken to assess the efficacy and safety of TCM
for AGA, and this meta-analysis concluded that the ef-
AGA is progressive hair loss in the frontotemporal region ficacy of CM therapies was significantly enhanced when
and top of the head after puberty, which seriously affects complemented with TCM. Despite this positive finding,
the appearance and brings great mental pressure and a the conclusion was not convincing because only two
psychological burden to patients, especially young people. outcomes were applied in the review. Moreover, because
The incidence rate of AGA across the world is on the rise, only 2 studies reported adverse events, the safety as-
with 30.2% in the Asians and higher in Caucasians [52]. sessment of TCM was restricted. Therefore, we rigorously
According to previous research, the main cause of AGA is performed an updated systematic review to evaluate the
genetic factors related to autosomal dominant polygenic effectiveness and safety of TCM.
inheritance and endocrine dysplasia; insomnia, mental This updated meta-analysis assessed the evidence from
pressure, mental disorders, and inappropriate diet play an 30 RCTs with a total 2615 AGA patients randomized to
important role in aggravating AGA symptoms [47]. Cur- receive additional TCM or CM between 2008 and 2019. The
rently, finasteride and minoxidil remain the first-line drugs main results included the following: (1) the TER of the TCM
for AGA. Because a large number of randomized placebo- group was strikingly higher than that of the CM group
controlled clinical trials have shown that finasteride and (OR � 3.34, 95% CI � 2.75–4.05, P < 0.00001), (2) the result
minoxidil significantly improved the hair density, hair of the TSS significantly favored the TCM group when
diameter, global photographic assessment (P < 0.05), and compared with the CM group (MD � –1.29; 95% CI � − 1.51,
plasma dihydrotestosterone levels [55–58], their curative − 1.06, P < 0.00001), (3) for common symptoms, patients in
effects are indisputable. However, because of side effects, a the TCM group benefited more than those in the CM group,
high recurrence rate, and persistent metabolic abnormal- (4) compared with patients treated with the same CM, the
ities of androgen-induced long-term medication, the effi- addition of TCM provoked a striking improvement in
cacy and safety of finasteride and minoxidil need further the microelement level (Fe2+, Zn2+, and Cu2+), (5) the
improvement. Additionally, AGA usually results in de- results across various subgroups were in great agreement,
pression and anxiety which immensely reduces the efficacy the benefits of TCM were significant, and no statistical
of finasteride and minoxidil. Therefore, finding effective difference was found between the TCM and CM groups
complementary therapies that significantly enhance the regarding the adverse events (OR � 0.55, 95% CI � 0.29–1.05,
effectiveness and lower the adverse events rate of P � 0.07).
8 Evidence-Based Complementary and Alternative Medicine

significant heterogeneity in the pooled data. The results of

Blinding of participants and personnel


the sensitivity analysis suggested that one study [36] greatly

Blinding of outcome assessment


Random sequence generation
reduced the heterogeneity from 71% to 0. By comparing it

Incomplete outcome data


with the other 6 trials, we found that it used different scales

Allocation concealment
for symptom scores, which directly led to high heteroge-

(performance bias)

Selective reporting
(reporting bias)
(detection bias)
(selection bias)

(selection bias)
neity. However, we selected this research because it met our

(attrition bias)

Other bias
inclusion criteria. Generally, the result showed that TCM
strikingly reduced the TSS by improving the itchy, greasy,
and dandruff levels.
Bao et al., 2016 ? ? ? – – + ?

Chien et al., 2017 + + + + – + +


4.2. Secondary Outcomes. The secondary outcomes com-
Dai, 2010 – – ? ? + ? ? prised common symptoms and microelement levels (Ca2+,
Fang, 2009 + + ? ? – + ? Fe2+, Zn2+, and Cu2+). Common symptoms were reported
in six relatively high-quality papers [27, 29, 34, 43, 50]. By
Gong, 2013 ? – – ? + ? ?
analyzing the common symptoms, we found that the
He and Liang, 2015 ? – – – ? ? + CHFs used in the six studies contained almost all kidney
Liang, 2012 ? ? ? ? + + ?
yang-tonifying herbs (Rehmanniae Radix) and blood-
activating herbs (Salviae Miltiorrhizae Radix), which are
Li et al., 2016 ? ? ? ? – ? ?
conventional herbs used to enhance immunity and pro-
Lin, 2017 + – – ? + + ? mote blood circulation for thousands of years in China.
Liu, 2008 – – – ? ? ? ?
Two studies [34, 37] reported that the microelement levels
(Fe2+, Zn2+, and Cu2+) of the TCM group were signifi-
Liu and Sun, 2017 + ? ? ? + + + cantly improved when compared with the CM group,
Mo, 2014 + ? ? ? + + + indicating that TCM played an important role in nour-
ishing hair by improving some microelement levels.
Sui, 2014 ? ? ? ? ? + ?
Additionally, the results of two studies [34, 42] showed
Wang, 2008 – ? ? ? + + ? that the serum testosterone level was greatly down-
Wang et al., 2010 + – – ? ? + ?
regulated when complemented with TCM containing
Salviae Miltiorrhizae Radix. Moreover, animal studies
Wang et al., 2012 ? ? ? ? ? ? –
suggested that Salviae Miltiorrhizae Radix significantly
Wang et al., 2018 ? ? ? ? + + + lowered the androgen level by inhibiting the expression of
SF-1 protein in testicular tissue [62] and steroid hormone
Wu et al., 2011 ? ? ? ? + + ?
synthesis [63, 64]. The possible mechanisms of CHFs in
Wu et al., 2013 ? ? ? ? ? ? ? the treatment of AGA were the promotion of hair growth
Xia and Liu, 2012 ? ? ? ? + ? ? by nourishing hair follicle cells and prevention of epilation
by consolidating the root of hair. Because most studies
Xiang, 2008 ? ? ? ? + + +
lack cellular and molecular parameters such as hormones,
Xiang, 2013 ? ? ? ? – + + microelements, and biochemical factors, at the cellular
Xie, 2015 ? – – – ? ? –
and molecular levels, the anti-AGA mechanism of TCM
warrants further investigation. In brief, it is likely that
Xi et al., 2009 ? ? ? ? + – ?
TCM through a multiple-target pathway, multilevel and
Xi et al., 2010 ? ? ? ? ? ? + holistic therapy, has shown definite benefits in the ad-
junctive treatment of AGA.
Xu et al., 2014 + ? ? ? ? + ?

Yang, 2016 + ? ? ? ? ? +
4.3. Subgroup Analysis. A valid subgroup analysis could
Yang et al., 2008 ? ? ? ? + + ?
improve the reliability of these results. In this meta-analysis,
Ye and Qi, 2016 ? ? ? ? + + ? a subgroup analysis was performed for the two primary
outcomes including the TER and TSS, to identify the dif-
Zhang, 2017 + ? ? ? + + +
ference between the subgroups. In terms of the TER, 22
Figure 2: Risk of bias assessment of the 30 articles. studies were selected and divided into five subgroups, in-
cluding TCM versus placebo, TCM versus finasteride, TCM
versus minoxidil, TCM + minoxidil versus minoxidil, and
4.1. Primary Outcome. In this meta-analysis, we included as TCM versus vitamin B6+ cystine. Since being approved by
many RCTs as possible to value the clinical effectiveness and the FDA in 1992, finasteride, as an effective inhibitor of type
safety of TCM therapies to acquire believable evidence for II 5αR, has been widely used for AGA [7]. It was reported
treating AGA. The results indicated that additional TCM that finasteride could decrease the androgen level of hair
significantly improved the TER by 21% when compared with follicle cells [65]. Minoxidil, another conventionally used
the CM group alone. Regarding the TSS (I2 � 71%), there was drug, may work by dilating blood vessels, improving the
Evidence-Based Complementary and Alternative Medicine 9

Experimental Control Odds ratio Odds ratio


Study or subgroup Weight (%)
Events Total Events Total M-H, fixed, 95% CI M-H, fixed, 95% CI
Bao et al., 2016 24 27 16 25 1.6 4.50 [1.05, 19.22]
Chien et al., 2017 9 17 2 15 0.9 7.31 [1.25, 42.81]
Dai, 2010 49 67 30 44 8.5 1.27 [0.55, 2.92]
Fang, 2009 32 34 28 33 1.5 2.86 [0.51, 15.90]
Gong, 2013 38 46 25 40 4.1 2.85 [1.05, 7.71]
He and Liang, 2015 49 51 30 49 1.0 15.52 [3.37, 71.39]
Li et al., 2016 98 112 46 73 6.1 4.11 [1.97, 8.56]
Liang, 2012 28 45 15 48 4.8 3.62 [1.54, 8.54]
Lin, 2017 40 43 30 43 1.8 5.78 [1.51, 22.10]
Liu and Sun, 2017 44 50 32 50 3.3 4.13 [1.47, 11.56]
Liu, 2008 54 60 38 60 3.3 5.21 [1.93, 14.07]
Mo, 2014 31 35 26 33 2.7 2.09 [0.55, 7.92]
Sui, 2014 41 46 34 46 3.2 2.89 [0.93, 9.03]
Wang, 2008 22 30 10 28 2.4 4.95 [1.62, 15.16]
Wang et al., 2010 62 83 23 45 6.6 2.82 [1.31, 6.07]
Wang et al., 2012 36 40 30 40 2.6 3.00 [0.85, 10.54]
Wang et al., 2018 37 43 25 43 3.0 4.44 [1.55, 12.74]
Wu et al., 2011 78 88 50 70 5.5 3.12 [1.35, 7.21]
Wu et al., 2013 43 56 24 38 5.8 1.93 [0.78, 4.77]
Xi et al., 2009 44 45 27 35 0.6 13.04 [1.54, 110.07]
Xi et al., 2010 22 36 13 30 4.8 2.05 [0.77, 5.50]
Xia and Liu, 2012 26 30 18 30 2.1 4.33 [1.20, 15.61]
Xiang, 2008 30 35 13 28 1.8 6.92 [2.08, 23.06]
Xiang, 2013 30 33 25 31 2.0 2.40 [0.54, 10.59]
Xie, 2015 31 33 24 32 1.3 5.17 [1.00, 26.60]
Xu et al., 2014 45 47 41 48 1.5 3.84 [0.75, 19.56]
Yang, 2016 34 40 27 40 3.5 2.73 [0.92, 8.13]
Yang et al., 2008 28 32 23 30 2.6 2.13 [0.55, 8.19]
Ye and Qi, 2016 37 50 28 50 6.3 2.24 [0.96, 5.20]
Zhang, 2017 32 42 23 42 4.8 2.64 [1.04, 6.73]

Total (95% CI) 1396 1219 100.0 3.34 [2.75, 4.05]


Total events 1174 776
Heterogeneity: chi2 = 21.18, df = 29 (P = 0.85); I2 = 0%
Test for overall effect: Z = 12.14 (P < 0.00001) 0.005 0.1 1 10 200
Favours (control) Favours (TCM)

Figure 3: Forest plot and meta-analysis of the TER.

Experimental Control Std. mean difference Std. mean difference


Study or subgroup Weight (%)
Mean SD Total Mean SD Total IV, random, 95% CI IV, random, 95% CI
Dai, 2010 6.81 3.96 67 10 4.47 44 15.8 –0.76 [–1.15, –0.37]
Fang, 2009 5.18 3.43 34 8.12 4.85 33 14.0 –0.69 [–1.19, –0.20]
Liu and Sun, 2017 1.62 1.01 50 2.68 1.08 50 15.4 –1.01 [–1.42, –0.59]
Mo, 2014 11.37 0.52 35 12.67 0.74 33 12.3 –2.02 [–2.61, –1.43]
Wu et al., 2013 7.43 3.16 56 9.63 4.1 38 15.3 –0.61 [–1.03, –0.19]
Xiang, 2008 7.077 5.662 27 10.02 6.959 28 13.3 –0.46 [–0.99, 0.08]
Xiang, 2013 2.39 1.56 33 3.37 1.747 31 13.9 –0.59 [–1.09, –0.08]
Total (95% CI) 302 257 100.0 –0.86 [–1.19, –0.53]
Heterogeneity: tau2 = 0.14; chi2 = 20.52, df = 6 (P = 0.002); I2 = 71%
Test for overall effect: Z = 5.10 (P < 0.00001) –4 –2 0 2 4
Favours (TCM) Favours (control)

Figure 4: Forest plot and meta-analysis of the TSS.

microcirculation around the follicle, increasing skin blood therapy. No significant difference was found between the
flow, promoting cell division, and prolonging hair follicle two subgroups (P � 0.66). Generally, the results among
growth [66]. However, the pharmacological mechanism of subgroups were inconsistent, as shown in Table 3.
vitamin B6 and cystine in treating hair loss was attributed to
the nourishment of follicle cells [67]. The result indicated
that additional TCM were more effective than CM alone. 4.4. CHFs. There were 29 CHFs used for the treatment of
With the TSS, two subgroups were introduced to determine AGA in this review. Two trials used the same CHF, but with
the difference between TCM alone and TCM combined different dosage forms (decoction in Xi et al. 2009 and pill
10 Evidence-Based Complementary and Alternative Medicine

Experimental Control Std. mean difference Std. mean difference


Study or subgroup Weight (%)
Mean SD Total Mean SD Total IV, random, 95% CI IV, random, 95% CI
Dai, 2010 1.22 1.52 67 1.91 2.02 44 18.0 –0.40 [–0.78, –0.01]
Fang, 2009 0.94 1.13 34 1.7 1.42 33 17.8 –0.59 [–1.08, –0.10]
Lin, 2017 0.37 0.12 43 3.48 0.24 43 10.7 –16.24 [–18.77, –13.72]
Mo, 2014 2.06 0.27 35 2.55 0.32 33 17.7 –1.64 [–2.19, –1.09]
Wang et al., 2018 1.2 0.7 43 2.4 0.7 43 17.8 –1.70 [–2.20, –1.20]
Yang, 2016 0.95 0.37 40 1.22 0.59 40 17.9 –0.54 [–0.99, –0.10]

Total (95% CI) 262 236 100.0 –2.60 [–3.88, –1.33]


2
Heterogeneity: tau = 2.31; chi2= 169.42, df = 5 (P < 0.00001); I2 = 97% –20 –10 0 10 20
Test for overall effect: Z = 4.00 (P < 0.0001) Favours (TCM) Favours (control)

(a)

Experimental Control Std. mean difference Std. mean difference


Study or subgroup Weight (%)
Mean SD Total Mean SD Total IV, random, 95% CI IV, random, 95% CI
Dai, 2010 2.03 1.95 67 3.64 1.69 44 21.1 –0.86 [–1.26, –0.47]
Lin, 2017 0.56 0.19 43 1.89 0.34 43 20.4 –4.79 [–5.63, –3.94]
Mo, 2014 0.91 0.21 35 3.8 0.26 33 16.7 –12.13 [–14.28, –9.97]
Wang et al., 2018 0.9 0.5 43 2.4 0.6 43 20.8 –2.69 [–3.28, –2.10]
Yang, 2016 0.95 0.37 40 1.22 0.59 40 21.0 –0.54 [–0.99, –0.10]

Total (95% CI) 228 203 100.0 –3.86 [–5.77, –1.95]


2
Heterogeneity: tau = 4.48; chi2= 194.23, df = 4 (P < 0.00001); I2 = 98% –50 –25 0 25 50
Test for overall effect: Z = 3.96 (P < 0.0001) Favours (TCM) Favours (control)

(b)

Experimental Control Std. mean difference Std. mean difference


Study or subgroup Weight (%)
Mean SD Total Mean SD Total IV, random, 95% CI IV, random, 95% CI
Dai, 2010 1.5 0.5 67 2.09 1.69 44 18.0 –0.52 [–0.90, –0.13]
Fang, 2009 0.88 1.12 34 1.82 1.36 33 17.8 –0.75 [–1.24, –0.25]
Lin, 2017 0.84 0.33 43 2.34 0.75 43 17.6 –2.57 [–3.14, –1.99]
Mo, 2014 1.14 0.21 35 3.97 0.23 33 11.1 –12.72 [–14.97, –10.47]
Wang et al., 2018 1.1 0.6 43 2.2 0.6 43 17.7 –1.82 [–2.32, –1.31]
Yang, 2016 0.92 0.46 40 1.73 0.8 40 17.8 –1.23 [–1.71, –0.75]

Total (95% CI) 262 236 100.0 –2.63 [–3.83, –1.43]

Heterogeneity: tau2 = 2.03; chi2 = 141.72, df = 5 (P < 0.00001); I2 = 96% –10 –5 0 5 10


Test for overall effect: Z = 4.31 (P < 0.0001) Favours (TCM) Favours (control)

(c)

Figure 5: Forest plot and meta-analysis of common symptoms including (a) itchy scalp level, (b) greasy scalp level, and (c) dandruff level.

in Xi et al. 2010). Although the CHFs used for AGA in most 333, 55.3%). Although thousands of medicinal herbs are
of the included documents were varied, some herbs such as included in the “Chinese pharmacopoeia,” TCM for the
Salviae Miltiorrhizae Radix and Rehmanniae Radix were treatment of androgenetic alopecia is highly dependent on
frequently prescribed in the 29 CHFs. According to the these 15 herbs. In addition, Rehmanniae Radix, Polygoni
statistical analysis of all ingredients used in the 29 CHFs, we multiflori Radix, Ecliptae Herba, Platycladi Cacumen, and
determined the top fifteen frequently used herbs and their Ligustri Lucidi Fructus have been specifically used for hair
usage frequency and listed their efficacies in TCM theory. problems by TCM physicians for thousands of years and
The results showed that the top fifteen commonly used are widely recorded in Chinese medicine classic texts.
herbs were Salviae Miltiorrhizae Radix (n � 18), Rehman- Modern medicine studies the workings of the human body
niae Radix (n � 17), Poria (n � 17), Polygoni multiflori by precisely measuring its cellular, protein, molecular,
Radix (n � 15), Ligustri Lucidi Fructus (n � 15), Ecliptae receptor, target, genetic, and other parameters and em-
Herba (n � 13), Crataegi Fructus (n � 12), Angelicae phasizes the treatment of diseases, while TCM pays more
Sinensis Radix (n � 12), Glycyrrhizae Radix et Rhizoma attention to the integrity of the human body and em-
(n � 12), Platycladi Cacumen (n � 11), Alismatis Rhizoma phasizes comprehensive conditioning and personalized
(n � 9), Chuanxiong Rhizoma (n � 9), Mori Fructus (n � 8), medicine. Although they use different strategies, their ul-
Cuscutae Semen (n � 8), and Moutan Cortex (n � 8), and timate goal is the same. Thus, there are some differences
the fifteen herbs in bold represent a large proportion (184/ between formulations. However, the statistical result
Evidence-Based Complementary and Alternative Medicine 11

Experimental Control Mean difference Mean difference


Study or subgroup Weight (%)
Mean SD Total Mean SD Total IV, random, 95% CI IV, random, 95% CI
Wang et al., 2018 539.6 10.5 43 527.8 10.7 43 73.5 11.80 [7.32, 16.28]
Zang, 2017 564.26 76.15 42 529.17 71.48 42 26.5 35.09 [3.50, 66.68]

Total (95% CI) 85 85 100.0 17.98 [–2.17, 38.14]


–100 –50 0 50 100
Heterogeneity: tau2 = 138.74; chi2 = 2.05, df = 1 (P < 0.15); I2 = 51%
Favours (control) Favours (TCM)
Test for overall effect: Z = 1.75 (P < 0.08)
(a)

Experimental Control Mean difference Mean difference


Study or subgroup Weight (%)
Mean SD Total Mean SD Total IV, random, 95% CI IV, random, 95% CI
Wang et al., 2018 20.5 0.7 43 17.9 0.9 43 89.9 2.60 [2.26, 2.94]
Zang, 2017 21.38 2.59 42 18.26 2.15 42 10.1 3.12 [2.10, 4.14]

Total (95% CI) 85 85 100.0 2.65 [2.33, 2.98]

Heterogeneity: chi2 = 0.90, df = 1 (P = 0.34); I2 = 0% –4 –2 0 2 4


Test for overall effect: Z = 16.09 (P < 0.00001) Favours (control) Favours (TCM)

(b)

Experimental Control Mean difference Mean difference


Study or subgroup Weight (%)
Mean SD Total Mean SD Total IV, random, 95% CI IV, random, 95% CI
Wang et al., 2018 209.6 8.7 43 187.5 9.6 43 62.3 22.10 [18.23, 25.97]
Zang, 2017 215.96 21.04 42 202.54 23.35 42 37.0 13.42 [4.14, 22.70]

Total (95% CI) 85 85 100.0 18.83 [10.58, 27.07]


2=
Heterogeneity: tau 24.50; chi2 =
2.86, df = 1 (P = 0.09); I2 = 65% –50 –25 0 25 50
Test for overall effect: Z = 4.51 (P < 0.00001) Favours (control) Favours (TCM)

(c)

Experimental Control Mean difference Mean difference


Study or subgroup Weight (%)
Mean SD Total Mean SD Total IV, random, 95% CI IV, random, 95% CI
Wang et al., 2018 8.9 0.8 43 8.1 0.6 43 69.7 0.80 [0.50, 1.10]
Zang, 2017 9.14 1.35 42 8.46 0.65 42 30.3 0.68 [0.23, 1.13]

Total (95% CI) 85 85 100.0 0.76 [0.51, 1.01]

Heterogeneity: tau2 = 0.00; chi2 = 0.19, df = 1 (P < 0.66); I2 = 0% –2 –1 0 1 2


Test for overall effect: Z = 6.00 (P < 0.00001) Favours (control) Favours (TCM)

(d)

Figure 6: Forest plot and meta-analysis of microelement levels including (a) Ca2+, (b) Fe2+, (c) Zn2+, and (d) Cu2+.

suggested they use most of the same herbs. In brief, the 29 randomization, but only nine studies described a specific
CHFs prescribed for treating AGA, based on the basic randomization method. Additionally, the detailed blin-
theory of TCM, were generally consistent, which further ded assessments were not reported in most documents
explains the prescription regularity of TCM for AGA and except two studies (Chien et al. 2017; Fang. 2009), which
provides, to some extent, a theoretical basis for the research may have exerted a potential impact on the objectivity of
and development of new CHFs for the adjuvant treatment the AGA outcomes. Second, most studies had small
of AGA, as shown in Tables 4 and 5. sample sizes with relatively low-quality designs, which
may have led to overvaluing the benefit of TCM. In
addition, the composition, dosage form, and treatment
4.5. Limitations and Critical Considerations. Several limi- duration of the TCM groups varied, which led to sig-
tations of our meta-analysis should be highlighted. First, nificant heterogeneity among the studies. Third, almost
because we only searched the main English and Chinese half of the studies had only a few endpoint indicators, and
databases, some studies meeting our inclusion criteria many outcomes except TER and TSS were less than six
published in other languages or databases may be ex- studies. In addition, the evaluation of the therapeutic
cluded. All included trials declared that they employed effect was somewhat subjective by using common
12 Evidence-Based Complementary and Alternative Medicine

Experimental Control Odds ratio Odds ratio


Study or subgroup Weigth (%)
Events Total Events Total M-H, fixed, 95% CI M-H, fixed, 95% CI
Chien et al., 2017 0 17 0 15 Not estimable
Dai, 2010 0 67 0 44 Not estimable
Fang, 2009 1 34 2 33 7.8 0.47 [0.04, 5.44]
He and Liang, 2015 0 51 2 49 10.0 0.18 [0.01, 3.94]
Li et al., 2016 3 112 0 73 2.3 4.70 [0.24, 92.31]
Liang, 2012 0 45 0 48 Not estimable
Liu and Sun, 2017 1 50 1 50 3.9 1.00 [0.06, 16.44]
Mo, 2014 0 35 0 33 Not estimable
Wang, 2008 0 30 0 28 Not estimable
Wang et al., 2010 2 83 0 45 2.5 2.79 [0.13, 59.41]
Wu et al., 2013 0 56 0 38 Not estimable
Xi et al., 2009 0 45 0 35 Not estimable
Xiang, 2008 0 35 0 28 Not estimable
Xiang, 2013 2 33 4 31 15.4 0.44 [0.07, 2.57]
Xie, 2015 3 33 8 32 29.3 0.30 [0.07, 1.26]
Xu et al., 2014 0 47 0 0 Not estimable
Yang, 2016 0 40 4 40 17.6 0.10 [0.01, 1.92]
Yang et al., 2008 3 32 3 30 11.1 0.93 [0.17, 5.02]

Total (95% CI) 845 652 100.0 0.55 [0.29, 1.05]


Total events 15 24
Heterogeneity: chi2 = 6.16, df = 1 (P = 0.63); I2 = 0%
0.001 0.1 1 10 1000
Test for overall effect: Z = 1.82 (P = 0.07)
Favours (TCM) Favours (control)

Figure 7: Forest plot and meta-analysis of adverse events between the TCM and control groups.

Meta-analysis estimates, given named study is omitted


Lower CI Limit Estimate Upper CI Limit
Bao et al (2016)
Chien et al (2017)
Dai (2010)
Fang (2009)
Gong (2013)
He and Liang (2015)
Liu (2008)
Liu and Sun (2017)
Lin (2017)
Li et al (2016)
Liang (2012)
Mo (2014)
Sui (2014)
Wu et al (2013)
Wu et al (2011)
Wang et al (2012)
Wang et al (2010)
Wang et al (2018)
Wang (2008)
Xia and Liu (2012)
Xiang (2013)
Xu et al (2014)
Xie (2015)
Xiang (2008)
Xi et al (2009)
Xi et al (2010)
Yang et al (2008)
Yang (2016)
Ye and Qi (2016)
Zhang (2017)

2.63 2.75 3.34 4.05 4.31


(a)
Figure 8: Continued.
Evidence-Based Complementary and Alternative Medicine 13

Meta-analysis estimates, given named study is omitted


Lower CI Limit Estimate Upper CI Limit
Dai (2010)

Fang (2009)

Liu and Sun (2017)

Mo (2014)

Wu et al (2013)

Xiang (2008)

Xiang (2013)

–1.30 –1.20 –0.87 –0.53 –0.45


(b)

Figure 8: Sensitivity analysis plot of (a) TER and (b) TSS.

4
3

3
Standardized effect

2
Log OR

2 1

1 0

0 –1
0 1 2 3 0 0.5 1
Precision –esLogES
(a) (b)

Figure 9: (a) Egger’s publication bias and (b) filled funnel plot of TER.

Table 3: Subgroup analysis.


Subgroups Trials Effects model Pooled effect 95% CI P value
TER
TCM versus placebo 3 Fixed OR 3.55 1.83–6.88 0.0002
TCM versus finasteride 7 Fixed OR 2.58 1.83–3.64 <0.00001
TCM versus minoxidil 2 Fixed OR 5.87 2.30–14.96 0.0002
TCM + minoxidil versus minoxidil 3 Fixed OR 3.46 1.86–6.44 <0.0001
TCM versus vitamin B6+ cystine 7 Fixed OR 3.26 2.23–4.78 <0.00001
Total 95% 22 Fixed OR 3.14 2.53–3.90 <0.00001
Test for subgroup differences: chi-square � 3.22. df � 4 (P � 0.52). I2 � 0%
TSS
TCM versus conventional medicine 4 Random MD-2.07 –3.12, –1.12 0.0001
TCM + conventional medicine versus
3 Random MD-1.19 –1.8, –0.58 0.0001
conventional medicine
Total 95% 7 Random MD-1.46 –1.91, –1.01 <0.00001
Test for subgroup differences: chi-square � 0.2. df � 1 (P � 0.66). I2 � 0%

symptoms. Fourth, a certain publication bias existed in meta-analysis, the included trials were highly compara-
the 30 documents. However, although all these de- ble, and we strictly applied the inclusion criteria and
ficiencies may undermine the quality of evidence of this followed the guidelines. Since the patients of selected
14 Evidence-Based Complementary and Alternative Medicine

Table 4: The details of the 30 Chinese herbal formulas.


Study Formula Ingredients/percentages Preparation methods
Salviae Miltiorrhizae Radix (1.7%),
Polygoni multiflori Radix (1.25%),
Sophorae Flavescentis Radix (1.25%),
ShengFa Zanthoxylum bungeanum (0.8%), AES (1) Diacolation with 5000 ml 95% ethanol
Yang et al. [24]
Lotion (15%), AS (5%), BS-12(5%), inorganic (2) Concentrated to a thin extract
additive (10%), glycol distearate (3%),
silicone oil (1%), flavours (1%), water
(53%)
Rehmanniae Radix, Angelicae Sinensis
BeauTop Produced by Sun Ten Pharmaceutical
Chien et al. [25] Radix, Ecliptae Herba, Ginseng Radix,
Tablet (Taipei, China)
Astragali Radix, Ligustri Fructus
Angelicae Sinensis Radix, Chuanxiong
YuFaYe Rhizoma, Zanthoxylum bungeanum Produced by Bawang Co. LTD
Liang [26]
Lotion Maxim, Carthami Flos, Zingiberis (Guangzhou, China)
Rhizoma
Rehmanniae Radix (15 g), Salviae
Miltiorrhizae Radix (15 g), Platycladi
Cacumen (15 g), Poria (10 g), Crataegi
Fructus (15 g), Alismatis Rhizoma (10 g),
YiRen QuShi
Yang [27] Moutan Cortex (10 g), Lycopi Herba Decocted with water
Decoction
(10 g), Acori Tatarinowii Rhizoma (10 g),
Artemisiae Scopariae Herba (10 g),
Chaenomelis Fructus (10 g), Liuyi powder
(10 g), Coicis Semen (10 g)
Angelicae Sinensis Radix (15 g), Polygoni
multiflori Radix (15 g), Platycladi
TuoFaFang Cacumen (15 g), Chuanxiong Rhizoma
Wu et al. [28] Decocted with water
Decoction (15 g), Cinnamomi Ramulus (15 g), Viticis
Fructus (15 g), Puerariae Lobatae Radix
(30 g)
Rehmanniae Radix (15 g), Salviae
Miltiorrhizae Radix (15 g), Chuanxiong
Rhizoma (10 g), Platycladi Cacumen
(15 g), Crataegi Fructus (15 g),
QuShi ShengFaFang
Dai [29] Glycyrrhizae Radix et Rhizoma (5 g), Decocted with water
Decoction
Poria (10 g), Alismatis Rhizoma (10 g),
Moutan Cortex (10 g), Chaenomelis
Fructus (10 g), Coicis Semen (15 g), Lycopi
Herba (10 g)
Rehmanniae Radix (15 g), Salviae
Miltiorrhizae Radix (15 g), Poria (10 g),
Platycladi Cacumen (15 g), Crataegi
Fructus (15 g), Alismatis Rhizoma (10 g),
QuShi ShengFa
Wu et al. [30] Moutan Cortex (10 g), Lycopi Herba Decocted with water
Decoction
(10 g), Acori Tatarinowii Rhizoma (10 g),
Artemisiae Scopariae Herba (10 g),
Chaenomelis Fructus (10 g), Liuyi powder
(10 g), Coicis Semen (15 g)
Salviae Miltiorrhizae Radix (20 g),
Polygoni multiflori Radix (15 g),
Glycyrrhizae Radix et Rhizoma (6 g),
Crataegi Fructus (15 g), Poria (30 g),
QuZhi GuTuoYin Ligustri Lucidi Fructus (15 g), Moutan
Sui [31] Decocted with water
Decoction Cortex (10 g), Cuscutae Semen (12 g),
Sophorae Flavescentis Radix (10 g),
Astragali Radix (15 g), Polyporus (15 g),
Lycii Fructus (10 g), Psoraleae Fructus
(12 g), Ziziphi Spinosae Semen (15 g)
Evidence-Based Complementary and Alternative Medicine 15

Table 4: Continued.
Study Formula Ingredients/percentages Preparation methods
Rehmanniae Radix (20 g), Chuanxiong
Rhizoma (15 g), Alismatis Rhizoma
(15 g), Mori Fructus (15 g), Polyporus
(25 g), Tuber Fleeceflower Stem (25 g),
QuShi JianFaYin
Wang et al. [32] Dioscoreae Tokoro Rhizoma (25 g), Decocted with water
Decoction
Plantaginis Semen (15 g), Dictamni Cortex
(25 g), Atractylodis Macrocephalae
Rhizoma (25 g), Halloysitum Rubrum
(20 g)
Rehmanniae Radix (12–30 g), Salviae
Miltiorrhizae Radix (15–30 g), Angelicae
Sinensis Radix (10 g), Crataegi Fructus
(10 g), Chuanxiong Rhizoma (10 g),
Alismatis Rhizoma (10 g), Cuscutae
ShengFa Pill Semen (12 g), Chaenomelis Fructus (6 g),
Li et al. [33] Decocted with water
Decoction Ziziphi Spinosae Semen (15–20 g),
Paeoniae Radix Alba (12 g), Polygoni
Multiflori Caulis (15 g), Carthami Flos
(6–10 g), Cimicifugae Rhizoma (3 g),
Atractylodis Macrocephalae Rhizoma
(10–15 g)
Salviae Miltiorrhizae Radix (30 g),
Polygoni multiflori Radix (15 g), Poria
(20 g), Crataegi Fructus (15 g), Ligustri
Lucidi Fructus (15 g), Glycyrrhizae Radix
Wang and Zhang QuZhi ShengFaYin et Rhizoma (10 g), Mori Fructus (15 g),
Decocted with water
[34] Decoction Alismatis Rhizoma (15 g), Moutan
Cortex (15 g), Taraxaci Herba (25 g),
Oldenlandia diffusa Herba (30 g), Coicis
Semen (40 g), Gardenia jasminoides (20 g),
Dictamni Cortex (20 g)
Rehmanniae Radix (200 g), Ligustri
Lucidi Fructus (150 g), Chuanxiong
Rhizoma (40 g), Ecliptae Herba (100 g),
Produced by Jingchuan Hospital of
DiHuang ShengFaLing Carthami Flos (40 g), Psoraleae Fructus
He and Liang [35] Traditional Chinese Medicine, Gansu,
Decoction (150 g), Cordyceps (20 g), Ginseng Radix
China
(50 g), Achyranthis bidentate Radix (50 g),
Morindae Officinalis Radix (120 g),
Polygonati Rhizoma (120 g)
Platycladi Cacumen, Garden Balsam
Produced by Hunan University of
QuZhi ShengFa Stem, Sophorae Flavescentis Radix,
Mo [36] Traditional Chinese Medicine, Changsha,
Lotion Polygonati Rhizoma, Gleditsiae Fructus,
China
0.2% sodium benzoate
Rehmanniae Radix (15 g), Salviae
Miltiorrhizae Radix (20 g), Polygoni
multiflori Radix (20 g), Poria (10 g),
Ligustri Lucidi Fructus (20 g),
JiaWei ErZhiWan Glycyrrhizae Radix et Rhizoma (6 g),
Zhang [37] Decocted with water
Decoction Alismatis Rhizoma (10 g), Moutan
Cortex (10 g), Ecliptae Herba (20 g),
Paeoniae Radix Alba (15 g), Sesami Semen
Nigrum (15 g), Juglandis Semen (12 g),
Corni Fructus (12 g)
16 Evidence-Based Complementary and Alternative Medicine

Table 4: Continued.
Study Formula Ingredients/percentages Preparation methods
Rehmanniae Radix (20 g), Angelicae
Sinensis Radix (10 g), Polygoni multiflori
Radix (15 g), Poria (10 g), Ligustri Lucidi
Fructus (20 g), Platycladi Cacumen
YiShen ShengFaTang
Liu and Sun [38] (15 g), Glycyrrhizae Radix et Rhizoma Decocted with water
Decoction
(10 g), Cuscutae Semen (20 g), Ecliptae
Herba (15 g), Lycii Fructus (10 g),
Polygonati Rhizoma (15 g), Ziziphi
Spinosae Semen (30 g)
Rehmanniae Radix (30 g), Salviae
Miltiorrhizae Radix (15 g), Angelicae
Sinensis Radix (20 g), Polygoni multiflori
Radix (20 g), Poria (20 g), Ligustri Lucidi
Fructus (10 g), Crataegi Fructus (15 g),
Chuanxiong Rhizoma (20 g),
Chuanxiong Rhizoma (20 g), Mori
Fructus (20 g), Ecliptae Herba (10 g),
Gao Fang
Bao et al. [39] Psoraleae Fructus (20 g), Dioscoreae Decocted with water
Decoction
Rhizoma (15 g), Paeoniae Radix Alba
(20 g), Bupleuri Radix (15 g), Gastrodiae
Rhizoma (10 g), Uncariae Ramulus Cum
Uncis (10 g), Acori Tatarinowii Rhizoma
(20 g), Atractylodis Macrocephalae
Rhizoma (30 g), Citri Reticulatae
Pericarpium (20 g), Massa Medicata
Fermentata (15 g)
Salviae Miltiorrhizae Radix (30 g),
Angelicae Sinensis Radix (15 g), Polygoni
multiflori Radix (15 g), Poria (15 g),
Ligustri Lucidi Fructus (30 g),
BuShen ZiYing Fang
Wang [40] Glycyrrhizae Radix et Rhizoma (10 g), Decocted with water
Decoction
Mori Fructus (15 g), Cuscutae Semen
(15 g), Ecliptae Herba (30 g), Lycii Fructus
(10 g), Astragali Radix (15 g), Taxilli Herba
(15 g)
Salviae Miltiorrhizae Radix (30 g),
Polygoni multiflori Radix (30 g), Ligustri
Lucidi Fructus (30 g), Crataegi Fructus
(30 g), Glycyrrhizae Radix et Rhizoma
ZhaQu PinWeiSan He Er (6 g), Platycladi Cacumen (30 g), Ecliptae
Xiang [41] ZhiWan Herba (15 g), Massa Medicata Fermentata Decocted with water
Decoction (20 g), Sophorae Flos (30 g), Atractylodis
Rhizoma (10 g), Magnoliae officinalis
Cortex (15 g), Citri Reticulatae
Pericarpium (15 g), Acori Tatarinowii
Rhizoma (10 g)
Tanshinone Produced by Hebei Xinglong Xili
Xiang [42] Salviae Miltiorrhizae Radix
Capsule Pharmaceutical Co. LTD, China
Rehmanniae Radix (12 g), Salviae
Miltiorrhizae Radix (15 g), Angelicae
Sinensis Radix (15 g), Polygoni multiflori
Radix (18 g), Poria (12 g), Platycladi
Qibao beards folk
Cacumen (10 g), Ligustri Lucidi Fructus
Lin [43] prescription Decocted with water
(18 g), Mori Fructus (18 g), Cuscutae
Decoction
Semen (15 g), Lycii Fructus (10 g),
Achyranthis Bidentatae Radix (12 g),
Scutellariae Radix (12 g), Astragali Radix
(15 g)
Evidence-Based Complementary and Alternative Medicine 17

Table 4: Continued.
Study Formula Ingredients/percentages Preparation methods
Rehmanniae Radix (12 g), Salviae
Miltiorrhizae Radix (12 g), Polygoni
multiflori Radix (12 g), Coptidis Rhizoma
JiaWei HuangLian EJiao
Gong [44] (12 g), Sophorae Flavescentis Radix (12 g), Decocted with water
Decoction
Paeoniae Radix Alba (12 g), Scutellariae
Radix (9 g), Gastrodiae Rhizoma (9 g),
Asini Corii Colla (10 g), Hen egg yolk (2#)
Rehmanniae Radix (20 g), Salviae
Miltiorrhizae Radix (20 g), Polygoni
multiflori Radix (15 g), Platycladi
Cacumen (15 g), Crataegi Fructus (20 g),
Poria (20 g), Glycyrrhizae Radix et
GuShen ShengFaTang
Xi et al. [45] Rhizoma (6 g), Ligustri Lucidi Fructus Decocted with water
Decoction
(20 g), Mori Fructus (20 g), Ecliptae
Herba (15 g), Taraxaci Herba (20 g),
Concha ostreae (30 g), Mori Cortex (15 g),
Oldenlandia diffusa Herba (15 g), Bupleuri
Radix (10 g)
Rehmanniae Radix (15 g), Salviae
Miltiorrhizae Radix (20 g), Angelicae
Sinensis Radix (15 g), Polygoni multiflori
Radix (15 g), Poria (30 g), Ligustri Lucidi
Fructus (15 g), Glycyrrhizae Radix et
Rhizoma (20 g), Chuanxiong Rhizoma
(20 g), Mori Fructus (20 g), Cuscutae
ZiNi ZiShen YangXue
Semen (15 g), Ecliptae Herba (15 g),
Xia and Liu [46] ShengFaTang Decocted with water
Dioscoreae Rhizoma (15 g), Paeoniae
Decoction
Radix Alba (10 g), Astragali Radix (15 g),
Spatholobi Caulis (20 g), Ziziphi Spinosae
Semen (20 g), Tuber Fleeceflower Stem
(20 g), Corni Fructus (20 g), Lycii Fructus
(20 g), Eucommiae Cortex (15 g),
Polygonati Rhizoma (15 g), Taraxaci Herba
(20 g)
Angelicae Sinensis Radix, Polygoni
YangXue ShengFa HeJi multiflori Radix, Poria, Cuscutae Semen, Produced by Kunming Hospital of
Ye and Qi [47]
Decoction Lycii Fructus, Achyranthis Bidentatae Traditional Chinese Medicine
Radix, Psoraleae Fructus
Rehmanniae Radix, Salviae
Miltiorrhizae Radix, Polygoni multiflori
Radix, Platycladi Cacumen, Crataegi
Produced by Hunan University of
QuZhi ShengFa Fructus, Poria, Glycyrrhizae Radix et
Xi et al. [48] Traditional Chinese Medicine, Changsha,
Pill Rhizoma, Ligustri Lucidi Fructus, Mori
China
Fructus, Ecliptae Herba, Taraxaci Herba,
Ostreae Concha, Mori Cortex,
Oldenlandia diffusa Herba, Bupleuri Radix
Poria (30 g), Crataegi Fructus (30 g),
Moutan Cortex (10 g), Scutellariae Radix
(15 g), Platycodonis Radix (6 g), Taraxaci
Fukang mixture Herba (30 g), Bupleuri Radix (10 g),
Wang et al. [49] Decocted with water
Decoction Oldenlandia diffusa Herba (20 g),
Paeoniae Radix Rubra (30 g), Sophorae
Flos (10 g), Dictamni Cortex (15 g),
Prunellae Spica (10 g), gypsum (30 g)
18 Evidence-Based Complementary and Alternative Medicine

Table 4: Continued.
Study Formula Ingredients/percentages Preparation methods
Rehmanniae Radix (20 g), Angelicae
Sinensis Radix (15 g), Ligustri Lucidi
Fructus (10 g), Moutan Cortex (15 g),
ShengFa Cuscutae Semen (20 g), Ecliptae Herba
Fang [50] Decocted with water
Decoction (30 g), Scutellariae Radix (15 g), Mori
Cortex (15 g), Schizonepetae Herba (15 g),
Saposhnikoviae Radix (10 g), Coicis Semen
(30 g), Cicadae Periostracum (10 g)
Rehmanniae Radix (15 g), Poria (15 g),
Glycyrrhizae Radix et Rhizoma (6 g),
Crataegi Fructus (10 g), Ligustri Lucidi
JianWei YiShen QuShi Fructus (15 g), Alismatis Rhizoma (10 g),
Xie [51] ShengFa Ecliptae Herba (15 g), Atractylodis Decocted with water
Decoction Macrocephalae Rhizoma (10 g),
Artemisiae Scopariae Herba (15 g),
Dictamni Cortex (10 g), Coicis Semen
(15 g)
Angelicae Sinensis Radix (15 g), Ligustri
Lucidi Fructus (15 g), Glycyrrhizae Radix
et Rhizoma (6 g), Poria (15 g), Platycladi
Cacumen (10 g), Chuanxiong Rhizoma
Quzhi Fangtuo shengfa ying
Liu [52] (15 g), Alismatis Rhizoma (10 g), Ecliptae Decocted with water
Decoction
Herba (15 g), Coicis Semen (15 g),
Puerariae Radix (15 g), Tribuli Fructus
(15 g), Dioscoreae Tokoro Rhizoma (10 g),
Rubi Fructus (15 g)
Salviae Miltiorrhizae Radix (60 g),
Psoraleae Fructus (60 g), Astragali Radix
ShengFa Ting
Xu et al. [53] (60 g), Carthami Flos (40 g), Zingiberis Diacolation with 1000 ml 60% ethanol
Decoction
Rhizoma (60 g), Cinnamomum camphora
(50 g)
Bold values represent the top 15 commonly used herbs, which have been listed in Table 5.

Table 5: Frequency of usage and TCM efficacy of the top 15 commonly used herbs.
Herbs Frequency TCM efficacy [68]
Salviae Miltiorrhizae Radix 18 Invigorating blood circulation to dissolve stasis
Rehmanniae Radix 17 Nourishing yin and tonifying blood
Poria 17 Inducing diuresis to alleviate edema
Polygoni multiflori Radix 15 Replenish blood and promoting hair growth
Ligustri Lucidi Fructus 15 Blacking hair
Ecliptae Herba 13 Nourishing liver and kidney and blacking hair
Crataegi Fructus 12 Promoting qi and dissipating stasis
Angelicae Sinensis Radix 12 Tonifying and activating blood
Glycyrrhizae Radix et Rhizoma 12 Tonifying spleen and replenishing qi
Platycladi Cacumen 11 Promoting hair growth and blacking
Alismatis Rhizoma 9 Dampness-draining diuretic
Chuanxiong Rhizoma 9 Activating blood and promoting qi
Mori Fructus 8 Nourishing yin and tonifying blood
Cuscutae Semen 8 Nourishing liver and kidney
Moutan Cortex 8 Activating blood and dissolving stasis
Total 184

studies were mainly from China, the conclusion of this and well-designed ethnic groupings should be conducted
meta-analysis may not be applicable to other ethnic in the future to provide more credible evidence on the
groups. Therefore, large sample trials with high-quality efficacy and safety of TCM for AGA.
Evidence-Based Complementary and Alternative Medicine 19

5. Conclusions [7] R. Rahimi-Ardabili, R. Pourandarjani, P. Habibollahi et al.,


“Finasteride induced depression, A prospective study,” BMC
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CM groups were significantly improved when com- of alopecia,” Expert Opinion on Pharmacotherapy, vol. 5, no. 4,
plemented with TCM. Therefore, TCM could be recom- pp. 933–940, 2004.
mended as an effective and safe complementary therapy for [9] E. A. Olsen, F. E. Dunlap, T. Funicella et al., “A randomized
clinical trial of 5% topical minoxidil versus 2% topical mi-
the treatment of AGA. However, long-term and higher-
noxidil and placebo in the treatment of androgenetic alopecia
quality RCTs are needed to overcome the limitations of the
in men,” Journal of the American Academy of Dermatology,
selected studies and more precisely interrogate the effec- vol. 47, no. 3, pp. 377–385, 2002.
tiveness and safety of TCM. [10] E. A. Olsen, D. Whiting, W. Bergfeld et al., “A multicenter,
randomized, placebo-controlled, double-blind clinical trial of
Conflicts of Interest a novel formulation of 5% minoxidil topical foam versus
placebo in the treatment of androgenetic alopecia in men,”
The authors declare no conflicts of interest. Journal of the American Academy of Dermatology, vol. 57,
no. 5, pp. 767–774, 2007.
[11] A. W. Lucky, D. J. Piacquadio, C. M. Ditre et al., “A ran-
Authors’ Contributions domized, placebo-controlled trial of 5% and 2% topical mi-
noxidil solutions in the treatment of female pattern hair loss,”
Qiang You and Lan Li contributed equally to this work. Journal of the American Academy of Dermatology, vol. 50,
Qiang You and Lan Li conceived the study, completed the no. 4, pp. 541–553, 2004.
manuscript, and performed the literature searches elec- [12] E. S. Friedman, P. M. Friedman, D. E. Cohen, and
tronically and manually. Yufen Yan and Suqin Xiong per- K. Washenik, “Allergic contact dermatitis to topical minoxidil
formed the study selection and data extraction. Fengqing Li solution: etiology and treatment,” Journal of the American
and Hao Fang assessed the risk of bias. Tian Gao and Xiao Academy of Dermatology, vol. 46, no. 2, pp. 309–312, 2002.
Ma made useful comments and performed language editing. [13] J. Shapiro and V. H. Price, “Hair regrowth,” Dermatologic
Hongping Chen and Youping Liu critically revised the Clinics, vol. 16, no. 2, pp. 341–356, 1998.
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[15] M. Jiang, C. Zhang, H. Cao, K. Chan, and A. Lu, “The role of
The authors would like to thank Tian Gao from the affiliated Chinese medicine in the treatment of chronic diseases in
Hospital, Chengdu University of TCM, and Xiao Ma from China,” Planta Medica, vol. 77, no. 9, pp. 873–881, 2011.
the Department of Pharmacy, Chengdu University of TCM, [16] C. S. Yang, G. Chen, and Q. Wu, “Recent scientific studies of a
for their useful comments and language editing which have traditional Chinese medicine, tea, on prevention of chronic
greatly improved the manuscript. They also appreciate the diseases,” Journal of Traditional and Complementary Medi-
support from the Chinese Natural Sciences Foundation (no. cine, vol. 4, no. 1, pp. 17–23, 2014.
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